+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-23871 | |||||||||
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タイトル | Paired helical tau filament extracted from PrP-CAA Patient brain tissue | tau filament | PHF Tau | |||||||||
マップデータ | 3 Angstrom resolution of PHF Tau from PrP-CAA | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / positive regulation of protein localization / regulation of chromosome organization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / apolipoprotein binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / microglial cell activation / synapse organization / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / microtubule cytoskeleton organization / cellular response to reactive oxygen species / SH3 domain binding / cytoplasmic ribonucleoprotein granule / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / cellular response to heat / protein-folding chaperone binding / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / DNA damage response / dendrite / protein kinase binding / enzyme binding / mitochondrion / DNA binding 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Human (ヒト) | |||||||||
手法 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | |||||||||
データ登録者 | Hoq M | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Acta Neuropathol / 年: 2021 タイトル: Structure of Tau filaments in Prion protein amyloidoses. 著者: Grace I Hallinan / Md Rejaul Hoq / Manali Ghosh / Frank S Vago / Anllely Fernandez / Holly J Garringer / Ruben Vidal / Wen Jiang / Bernardino Ghetti / 要旨: In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from ...In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) with a nonsense mutation in the PRNP gene that leads to early termination of translation of PrP (Q160Ter or Q160X), and Gerstmann-Sträussler-Scheinker (GSS) disease, with a missense mutation in the PRNP gene that leads to an amino acid substitution at residue 198 (F198S) of PrP. The clinical and neuropathologic phenotypes associated with these two mutations in PRNP are different; however, the neuropathologic analyses of these two genetic variants have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. We report that Tau filaments in PrP-CAA (Q160X) and GSS (F198S) are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA (Q160X), Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS (F198S), only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA (Q160X) and GSS (F198S) brains show the presence of post-translational modifications that are comparable to those seen in Tau aggregates from AD. Cryo-EM analysis reveals that the atomic models of the Tau filaments obtained from PrP-CAA (Q160X) and GSS (F198S) are identical to those of the Tau filaments from AD, and are therefore distinct from those of Pick disease, chronic traumatic encephalopathy, and corticobasal degeneration. Our data support the hypothesis that in the presence of extracellular amyloid deposits and regardless of the primary amino acid sequence of the amyloid protein, similar molecular mechanisms are at play in the formation of identical Tau filaments. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_23871.map.gz | 26.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-23871-v30.xml emd-23871.xml | 10.2 KB 10.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_23871_fsc.xml | 13.7 KB | 表示 | FSCデータファイル |
画像 | emd_23871.png | 102.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-23871 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23871 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_23871_validation.pdf.gz | 365.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_23871_full_validation.pdf.gz | 365.4 KB | 表示 | |
XML形式データ | emd_23871_validation.xml.gz | 12 KB | 表示 | |
CIF形式データ | emd_23871_validation.cif.gz | 15.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23871 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23871 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_23871.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | 3 Angstrom resolution of PHF Tau from PrP-CAA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.078 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Paired helical filament (PHF) from PrP-CAA
全体 | 名称: Paired helical filament (PHF) from PrP-CAA |
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要素 |
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-超分子 #1: Paired helical filament (PHF) from PrP-CAA
超分子 | 名称: Paired helical filament (PHF) from PrP-CAA / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: PHF tau in PrP-CAA, caused by the Q160X truncating mutation in PRNP |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 実験値: 55 kDa/nm |
-分子 #1: PHF Tau from PrP-CAA Patient
分子 | 名称: PHF Tau from PrP-CAA Patient / タイプ: other / ID: 1 / 分類: other |
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由来(天然) | 生物種: Human (ヒト) |
配列 | 文字列: QX |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | らせん対称体再構成法 |
試料の集合状態 | filament |
-試料調製
濃度 | 1 mg/mL |
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緩衝液 | pH: 7.4 |
糖包埋 | 材質: affinity tag |
グリッド | モデル: PELCO Ultrathin Carbon with Lacey Carbon / 材質: COPPER / メッシュ: 400 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: GATAN CRYOPLUNGE 3 |
詳細 | Filament extracted from frontal cortex of PrP-CAA patient brain |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 2004 / 平均電子線量: 1.067 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
-原子モデル構築 1
詳細 | Each model was refined using Rosetta |
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精密化 | 空間: RECIPROCAL / 温度因子: 24 / 当てはまり具合の基準: Fourier shell correlation |
得られたモデル | PDB-7mkf: |